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t-PA (Activase) in Acute Ischemic Stroke NINDS Study (1995) – Thrombolytic (t-PA) given IV within 3 hours of stroke symptom onset for treatment for acute ischemic stroke: Approved in US in 1996 Approved in US in 1996 Approval in Canada in 1999 Approval in Canada in 1999

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Canadian Stroke Strategy: Best Practice Recommendations 2010 All patients with disabling acute ischemic stroke who can be treated within 4.5 hours after symptom onset should be evaluated without delay to determine their eligibility for treatment with t-PA. All patients with disabling acute ischemic stroke who can be treated within 4.5 hours after symptom onset should be evaluated without delay to determine their eligibility for treatment with t-PA. All eligible patients should receive intravenous alteplase (t-PA) within one hour of hospital arrival All eligible patients should receive intravenous alteplase (t-PA) within one hour of hospital arrival door-to-needle time < 60 minutes door-to-needle time < 60 minutes

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Pre-Hospital Care: What’s New? WHEN CAN YOU TREAT WITH T-PA? WHEN CAN YOU TREAT WITH T-PA?

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Canadian Stroke Strategy: Best Practice Recommendations 2010 There is limited clinical trial data to support use of t-PA in the following circumstances: There is limited clinical trial data to support use of t-PA in the following circumstances: pediatric stroke pediatric stroke stroke patients > 80 years old with diabetes stroke patients > 80 years old with diabetes adults who do not meet current criteria for t- PA treatment adults who do not meet current criteria for t- PA treatment intra-arterial thrombolysis. intra-arterial thrombolysis. Obtain emergency consultation with a comprehensive stroke center

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BRAIN ATTACK TIME IS BRAIN! Get drug in fast! 1.9 million neurons are destroyed each minute treatment is delayed Goal - door to drug < 30 min

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Pathophysiology and t-PA Thrombus is formed during ischemic stroke. Thrombus is formed during ischemic stroke. Alteplase binds to fibrin in a thrombus: Alteplase binds to fibrin in a thrombus: converts plasminogen to plasmin converts plasminogen to plasmin initiates local fibrinolysis with minimal systemic effects. initiates local fibrinolysis with minimal systemic effects. Alteplase is cleared rapidly from circulating plasma by the liver. Alteplase is cleared rapidly from circulating plasma by the liver. >50% cleared within 5 min after infusion >50% cleared within 5 min after infusion 80% cleared within 10 min 80% cleared within 10 min

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Onset Time Onset Time = Time when patient was last seen well Onset Time = Time when patient was last seen well Requires detective skills Requires detective skills

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Preparing t-PA: 100mg Vial Holding Activase vial upside down, insert other end of transfer device into center of the stopper - Invert vials Holding Activase vial upside down, insert other end of transfer device into center of the stopper - Invert vials Allow vials to sit undisturbed till foam subsides (takes only seconds) Allow vials to sit undisturbed till foam subsides (takes only seconds) DO NOT SHAKE THE VIAL AS IT WILL DENATURE THE PROTEIN STRANDS DO NOT SHAKE THE VIAL AS IT WILL DENATURE THE PROTEIN STRANDS TIME IS BRAIN!

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Precautions!! Do not mix t-PA with any other medications. Do not mix t-PA with any other medications. Do not use IV tubing with infusion filters. Do not use IV tubing with infusion filters. All patients must be on a cardiac monitor All patients must be on a cardiac monitor When infusion is complete, saline lock IV and flush with N/S When infusion is complete, saline lock IV and flush with N/S t-PA must be used within 8 hours of mixing when stored at room temperature or within 24 hours if refrigerated t-PA must be used within 8 hours of mixing when stored at room temperature or within 24 hours if refrigerated

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APSS Recommended t-PA Protocol Antiplatelet/Anticoagulant Therapy No ASA, Clopidogrel, Aggrenox, Ticlopidine or other antiplatelet agents for 24 hours from start of t-PA No ASA, Clopidogrel, Aggrenox, Ticlopidine or other antiplatelet agents for 24 hours from start of t-PA No heparin, heparinoid or warfarin for 24 hours from start of t-PA No heparin, heparinoid or warfarin for 24 hours from start of t-PA CT or MRI must be completed and reviewed by physician to exclude intracranial hemorrhage prior to above therapy

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Adverse Effects of t-PA Angioedema Assess patient for signs of Assess patient for signs of of the tongue: Angioedema of the tongue: Swelling of tongue/lips Swelling of tongue/lips notify Physician immediately if swelling seen 1.3% of population Assess at 30, 45, 60, 75 minutes after tPA bolus. Once the t-PA infusion has finished the risk of angioedema falls off Patients on ACE inhibitors are at higher risk of angioedema

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Hypertension During Acute Stroke Occurrence: Systolic BP > 160mmHg is seen in over 60% stroke patients (Robinson et al, Cerebrovasc Dis., 1997) Systolic BP > 160mmHg is seen in over 60% stroke patients (Robinson et al, Cerebrovasc Dis., 1997) Often transient, lasting hours and in most patients does not require treatment. Often transient, lasting hours and in most patients does not require treatment. BP declines within first hours after stroke without medical treatment BP declines within first hours after stroke without medical treatment Systolic BP has been noted to drop ˜ 28% during first day, even without medications Systolic BP has been noted to drop ˜ 28% during first day, even without medications Oliveira-Filho et al; 2003; Neurology; 61:

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Dysphagia Dysphagia Greek word meaning - “disordered eating” Swallowing difficulties cause by damage to enervation of cranial nerves IX, X, XI. Impaired coordination of swallowing muscles or limited sensation in mouth/throat Occurs in ~ 55% new onset strokes ~ 50% of these do not recover normal swallow by 6 months Can cause airway obstruction and aspiration pneumonia Can cause airway obstruction and aspiration pneumonia Can lead to dehydration, weight loss, malnutrition Can lead to dehydration, weight loss, malnutrition Up to 70% dysphagic patients aspirate Up to 70% dysphagic patients aspirate up to 20% of those with stroke-related dysphagia die within first year up to 20% of those with stroke-related dysphagia die within first year